-- ASH data reinforce survival benefits of
front-line AYVAKIT® (avapritinib) use in patients with advanced SM
--
-- Bone density analyses reported in patients
with advanced SM underscore disease-modifying effects of AYVAKIT
--
CAMBRIDGE, Mass., Dec. 7, 2024
/PRNewswire/ -- Blueprint Medicines Corporation (Nasdaq: BPMC)
today announced data presentations that continue to demonstrate the
long-term clinical benefits of AYVAKIT® (avapritinib) in advanced
systemic mastocytosis (advanced SM), and reflect the company's
ongoing partnership with the SM community to redefine the future of
patient care – from improving diagnostic rates to raising the bar
on treatment outcomes. The datasets, which include one oral
presentation and three poster presentations, will be reported at
the 66th American Society of Hematology (ASH) Annual Meeting and
Exposition, taking place December
7-10 in San Diego.
"Systemic mastocytosis is associated with mast cell infiltration
across multiple organ systems, chronic inflammation caused by
immune dysregulation, unpredictable symptoms that may worsen over
time, and serious comorbidities such as osteoporosis, highlighting
the urgency to treat patients early in the course of their
disease," said Becker Hewes, M.D., Chief Medical Officer at
Blueprint Medicines. "AYVAKIT has fundamentally changed the
treatment paradigm by targeting the disease at its source, showing
prolonged survival outcomes for patients with advanced SM, as well
as durable symptom control and quality-of-life improvements for
patients with ISM. Based on the substantial datasets we have
amassed over more than a decade, and our continued collaboration
with the SM community, we have designed the HARBOR trial of
elenestinib – a next-generation KIT D816V inhibitor – to rigorously
assess a broad range of endpoints reflecting disease-modifying
impact."
Data reported at ASH highlight the survival benefits of
front-line AYVAKIT use in patients with advanced SM, and support
Blueprint Medicines' plans to evaluate novel clinical measures
indicative of disease modification – such as bone density and
biomarkers of chronic inflammation – in the registrational HARBOR
trial. Key results include:
- In pooled analyses from the PATHFINDER and EXPLORER trials,
treatment-naïve patients with advanced SM showed significant
survival benefits with AYVAKIT, when indirectly compared to
real-world outcomes for midostaurin.
- In the PATHFINDER trial, AYVAKIT led to sustained improvements
in bone density for advanced SM patients who had low bone mass at
baseline.
- In the PIONEER trial, patients with indolent SM (ISM) had
significant baseline levels of immune dysregulation relative to
healthy donors, reflecting the chronic inflammatory burden of the
disease.
Non-Invasive, Blood-Based Assay Identified KIT Mutations Not
Previously Detectable by Existing Tests
ASH data show that ultra-sensitive KIT testing in the peripheral
blood – a novel tool in clinical development that is more sensitive
than current commercially available methods – identified previously
undetected KIT mutations in a number of PIONEER trial patients.
Emerging clinical research with ultra-sensitive KIT assays suggest
SM may be more prevalent than previously thought.
An additional data presentation highlights the application of
machine learning techniques to analyze baseline, blood-based
parameters of Blueprint Medicines' clinical trial participants.
Following these analyses, a predictive model was developed to
distinguish between advanced SM and ISM, and its accuracy was
validated by an independent dataset from Dana-Farber Cancer
Institute.
Collectively, these data build on Blueprint Medicines'
collaborative efforts with clinical experts to improve and
accelerate how SM is diagnosed and treated.
Data presentations will be made available in the
"Science―Publications and Presentations" section of Blueprint
Medicines' website.
- Oral Presentation: Analysis of Avapritinib Clinical Trial Data
Generates a Highly Accurate Predictive Model for Advanced Systemic
Mastocytosis Versus Indolent Systemic Mastocytosis Based on
Peripheral Blood Testing (Abstract 107 – Saturday, December 7)
- Poster Presentation: Overall Survival and Duration of Treatment
in Patients with Advanced Systemic Mastocytosis Receiving
Avapritinib Versus Midostaurin or Best Available Therapy in a
Real-World Setting (Abstract 1801 – Saturday, December 7)
- Poster Presentation: Ultra-Sensitive KIT Testing Uncovers
Previously Undetected KIT Mutations in Patients with Indolent
Systemic Mastocytosis: Results from the PIONEER Trial (Abstract
3164 – Sunday, December 8)
- Poster Presentation: Disease-Modifying Effects of Avapritinib
in Patients with Advanced Systemic Mastocytosis: Improvements in
Bone Density (Abstract 4544 – Monday,
December 9)
- Publication-Only Abstract: Blood-Based Proteomics for Deeper
Insights into Indolent Systemic Mastocytosis: the PIONEER Trial
Experience (Abstract 6569)
About Systemic Mastocytosis
Systemic mastocytosis (SM) is a rare disease driven by the KIT
D816V mutation in about 95 percent of cases. Uncontrolled
proliferation and activation of mast cells result in chronic,
severe and often unpredictable symptoms across multiple organ
systems. The vast majority of those affected have indolent systemic
mastocytosis (ISM). A broad range of symptoms, including
anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog,
fatigue and bone pain, frequently persist in patients with ISM
despite treatment with multiple symptom-directed therapies. This
burden of disease can lead to a profound, negative impact on
quality of life. Patients often live in fear of severe, unexpected
symptoms, have limited ability to work or perform daily activities,
and isolate themselves to protect against unpredictable triggers.
Until 2023, there were no approved therapies for the treatment of
ISM.
A minority of patients have advanced SM, which encompasses a
group of high-risk SM subtypes including aggressive SM (ASM), SM
with an associated hematological neoplasm (SM-AHN) and mast cell
leukemia (MCL). In addition to mast cell activation symptoms,
advanced SM is associated with organ damage due to mast cell
infiltration and poor survival.
About AYVAKIT (avapritinib)
AYVAKIT (avapritinib) is approved by the U.S. Food and Drug
Administration (FDA) for the treatment of three indications: adults
with ISM, adults with advanced SM, including ASM, SM-AHN and MCL,
and adults with unresectable or metastatic gastrointestinal stromal
tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA
D842V mutations. Under the brand name AYVAKYT® (avapritinib), this
medicine is approved by the European Commission for the treatment
of adults with ISM with moderate to severe symptoms inadequately
controlled on symptomatic treatment, adults with ASM, SM-AHN and
MCL, after at least one systemic therapy, and adults with
unresectable or metastatic GIST harboring the PDGFRA D842V
mutation. The therapy is not recommended for the treatment of
patients with low platelet counts (less than 50,000/µL).
Please click here to see the full U.S. Prescribing Information
for AYVAKIT, and click here to see the European Summary of Product
Characteristics for AYVAKYT.
IMPORTANT SAFETY INFORMATION
Intracranial Hemorrhage — Serious intracranial hemorrhage (ICH)
may occur with AYVAKIT treatment; fatal events occurred in <1%
of patients. Overall, ICH (eg, subdural hematoma, ICH, and cerebral
hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT
in clinical trials. In Advanced SM patients who received AYVAKIT at
200 mg daily, ICH occurred in 2 of 75 patients (2.7%) who had
platelet counts ≥50 x 109/L prior to initiation of
therapy and in 3 of 80 patients (3.8%) regardless of platelet
counts. In ISM patients, no events of ICH occurred in the 246
patients who received any dose of AYVAKIT in the PIONEER study.
Monitor patients closely for risk factors of ICH which may
include history of vascular aneurysm, ICH or cerebrovascular
accident within the prior year, concomitant use of anticoagulant
drugs, or thrombocytopenia. Symptoms of ICH may include headache,
nausea, vomiting, vision changes, or altered mental status. Advise
patients to seek immediate medical attention for signs or symptoms
of ICH. Permanently discontinue AYVAKIT if ICH of any grade
occurs.
In Advanced SM patients, a platelet count must be performed
prior to initiating therapy. AYVAKIT is not recommended in Advanced
SM patients with platelet counts <50 x 109/L.
Following treatment initiation, platelet counts must be performed
every 2 weeks for the first 8 weeks. After 8 weeks of treatment,
monitor platelet counts every 2 weeks or as clinically indicated
based on platelet counts. Manage platelet counts of <50 x
109/L by treatment interruption or dose reduction.
Cognitive Effects — Cognitive adverse reactions can occur in
patients receiving AYVAKIT and occurred in 33% of 995 patients
overall in patients who received AYVAKIT in clinical trials
including: 28% of 148 Advanced SM patients (3% were Grade ≥3), and
7.8% of patients with ISM who received AYVAKIT + best supportive
care (BSC) versus 7.0% of patients who received placebo + BSC
(<1% were Grade 3). Depending on the severity and indication,
withhold AYVAKIT and then resume at same dose or at a reduced dose
upon improvement, or permanently discontinue.
Photosensitivity — AYVAKIT may cause photosensitivity reactions.
In all patients treated with AYVAKIT in clinical trials (n=1049),
photosensitivity reactions occurred in 2.5% of patients. Advise
patients to limit direct ultraviolet exposure during treatment with
AYVAKIT and for one week after discontinuation of treatment.
Embryo-Fetal Toxicity — AYVAKIT can cause fetal harm when
administered to a pregnant woman. Advise pregnant women of the
potential risk to a fetus. Advise females and males of reproductive
potential to use an effective method of contraception during
treatment with AYVAKIT and for 6 weeks after the final dose of
AYVAKIT. Advise women not to breastfeed during treatment with
AYVAKIT and for 2 weeks after the final dose.
Adverse Reactions — The most common adverse reactions (≥20%) in
patients with Advanced SM were edema, diarrhea, nausea, and
fatigue/asthenia.
The most common adverse reactions (≥10%) in patients with ISM
were eye edema, dizziness, peripheral edema, and flushing.
Drug Interactions — Avoid coadministration of AYVAKIT with
strong or moderate CYP3A inhibitors. If coadministration with a
moderate CYP3A inhibitor cannot be avoided in patients with
Advanced SM, reduce dose of AYVAKIT. Avoid coadministration of
AYVAKIT with strong or moderate CYP3A inducers. If contraception
requires estrogen, limit ethinyl estradiol to ≤20 mcg unless a
higher dose is necessary.
To report suspected adverse reactions, contact Blueprint
Medicines Corporation at 1-888-258-7768 or the FDA at
1-800-FDA-1088 or www.fda.gov/medwatch.
AYVAKIT is available in 25-mg, 50-mg, 100-mg and 200-mg
tablets.
Please click here to see the full U.S. Prescribing
Information for AYVAKIT.
About Blueprint Medicines
Blueprint Medicines is a global, fully integrated
biopharmaceutical company that invents life-changing medicines. We
seek to alleviate human suffering by solving important medical
problems in two core focus areas: allergy/inflammation and
oncology/hematology. Our approach begins by targeting the root
causes of disease, using deep scientific knowledge in our core
focus areas and drug discovery expertise across multiple
therapeutic modalities. We have a track record of success with two
approved medicines, including AYVAKIT®/AYVAKYT® (avapritinib) which
we are bringing to patients with systemic mastocytosis (SM) in the
U.S. and Europe. Leveraging our
established research, development, and commercial capability and
infrastructure, we now aim to significantly scale our impact by
advancing a broad pipeline of programs ranging from early science
to advanced clinical trials in mast cell diseases including SM and
chronic urticaria, breast cancer and other solid tumors. For more
information, visit www.BlueprintMedicines.com and follow
us on X (formerly Twitter; @BlueprintMeds)
and LinkedIn.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended, including, without limitation, statements
regarding the potential benefits of AYVAKIT for the treatment of
patients with advanced SM and ISM; statements regarding the HARBOR
trial for elenestinib; plans, strategies, timelines and
expectations for Blueprint Medicines' current or future approved
drugs and drug candidates; the potential benefits of any of
Blueprint Medicines' current or future approved drugs or drug
candidates in treating patients; and Blueprint Medicines' financial
performance, strategy, goals and anticipated milestones, business
plans and focus. The words "aim," "may," "will," "could," "would,"
"should," "expect," "plan," "anticipate," "intend," "believe,"
"estimate," "predict," "project," "potential," "opportunity,"
"continue," "target" and similar expressions are intended to
identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Any
forward-looking statements in this press release are based on
management's current expectations and beliefs and are subject to a
number of risks, uncertainties and important factors that may cause
actual events or results to differ materially from those expressed
or implied by any forward-looking statements contained in this
press release, including, without limitation, risks and
uncertainties related to: the delay of any current or planned
clinical trials or the development of the company's current or
future drug candidates; the company's ability to successfully
demonstrate the safety and efficacy of its drug candidates and gain
approval of its drug candidates on a timely basis, if at all; the
possibility that preclinical and clinical results for the company's
drug candidates may not support further development of such drug
candidates either as monotherapies or in combination with other
agents or may impact the anticipated timing of data or regulatory
submissions; the timing of the initiation of clinical trials and
trial cohorts at clinical trial sites and the possibility patient
enrollment rates may be delayed or slower than anticipated; the
actions of regulatory agencies and how this may affect the
initiation, timing and progress of clinical trials; the company's
ability to obtain, maintain and enforce patent and other
intellectual property protection for its products and current or
future drug candidates it is developing; and the success of the
company's current and future collaborations, partnerships or
licensing arrangements. These and other risks and uncertainties are
described in greater detail in the section entitled "Risk Factors"
in Blueprint Medicines' filings with the Securities and Exchange
Commission (SEC), including Blueprint Medicines' most recent Annual
Report on Form 10-K, as supplemented by its most recent Quarterly
Report on Form 10-Q and any other filings that Blueprint Medicines
has made or may make with the SEC in the future. Any
forward-looking statements contained in this press release
represent the company's views only as of the date hereof and should
not be relied upon as representing its views as of any subsequent
date. Except as required by law, the company explicitly disclaims
any obligation to update any forward-looking statements contained
in this press release as a result of new information, future events
or otherwise. Accordingly, readers are cautioned not to place undue
reliance on these forward-looking statements.
Trademarks
Blueprint Medicines, AYVAKIT, AYVAKYT and associated logos are
trademarks of Blueprint Medicines Corporation.
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